A preliminary investigation revealed that the major abnormal lipoprotein of cholestasis (commonly called LP-X) was present in perfusates of cholestatic rat livers. The first demonstration of LP-X within bile canaliculi was made in perfused cholestatic livers using a special block staining. We propose to use tracers of varying size to determine the pathway by which LP-X is transported from the bile canaliculi to the blood stream. By preparing single bilayer vesicles the same size as LP-X and injecting them into the perfusate and biliary passages, we propose to determine the origin of LP-X. Four additional lipoproteins with atypical or abnormal properties were also tentatively identified using this technique. All five of these abnormal or atypical plasma lipoproteins in perfusates of cholestatic rat livers appear to have counterparts in the plasma of human subjects with biliary obstruction. The proposed study would investigate this possibility by isolating each of these lipoproteins from perfusates and fully characterizing each. A systematic study of the nascent lipoproteins contained in the Golgi apparatus of cholestatic and control livers of sham-operated rats will be performed to determine whether the atypical very low density lipoprotein and low density lipoprotein of obstructive jaundice originate within the liver. The major apolipoprotein in perfusates of cholestatic and control livers of sham-operated rats will be measured with the expectation that new concepts of regulation of hepatic lipoprotein metabolism may be disclosed. Administration of clofibrate to humans and rats reportedly exacerbates the hypercholesterolemia of cholestasis. We propose to isolate, characterize and quantify the lipoproteins in the liver perfusates of clofibrate treated rats with biliary obstruction to determine if this combined treatment stimulates the hepatic secretion of lamellar plasma lipoproteins (LP-X and nascent HDL).